PMID- 24867303
OWN - NLM
STAT- MEDLINE
DCOM- 20150813
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 5
DP  - 2014
TI  - BBS4 is necessary for ciliary localization of TrkB receptor and activation by 
      BDNF.
PG  - e98687
LID - 10.1371/journal.pone.0098687 [doi]
LID - e98687
AB  - Primary cilia regulate an expanding list of signaling pathways in many different 
      cell types. It is likely that identification of the full catalog of pathways 
      associated with cilia will be necessary to fully understand their role in 
      regulation of signaling and the implications for diseases associated with their 
      dysfunction, ciliopathies. Bardet-Biedl Syndrome (BBS) is one such ciliopathy 
      which is characterized by a spectrum of phenotypes. These include neural defects 
      such as impaired cognitive development, centrally mediated hyperphagia and 
      peripheral sensory defects. Here we investigate potential defects in a signaling 
      pathway associated with neuronal function, brain derived neurotrophic factor 
      (BDNF) signaling. Upon loss of BBS4 expression in cultured cells, we observed 
      decreased phosphorylation and activation by BDNF of its target receptor, TrkB. 
      Assessment of ciliary localization revealed that, TrkB localized to the axonemes 
      or basal bodies of cilia only in the presence of BDNF. Axonemal localization, 
      specifically, was abrogated with loss of BBS4. Finally, we present evidence that 
      loss of the ciliary axoneme through depletion of KIF3A impedes activation of 
      TrkB. Taken together, these data suggest the possibility of a previously 
      uninvestigated pathway associated with perturbation of ciliary proteins.
FAU - Leitch, Carmen C
AU  - Leitch CC
AD  - Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School 
      of Medicine, Baltimore, Maryland, United States of America.
FAU - Zaghloul, Norann A
AU  - Zaghloul NA
AD  - Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School 
      of Medicine, Baltimore, Maryland, United States of America.
LA  - eng
GR  - K01DK092402/DK/NIDDK NIH HHS/United States
GR  - P30 DK079637/DK/NIDDK NIH HHS/United States
GR  - P30 DK072488/DK/NIDDK NIH HHS/United States
GR  - K01 DK092402/DK/NIDDK NIH HHS/United States
GR  - R01 DK102001/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140527
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (BBS4 protein, human)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (KIF3A protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Proteins)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
RN  - EC 3.6.4.4 (Kinesins)
SB  - IM
MH  - Axoneme/metabolism
MH  - Basal Bodies/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Line
MH  - Cilia/*metabolism
MH  - Humans
MH  - Kinesins/genetics
MH  - Membrane Glycoproteins/*metabolism
MH  - Microtubule-Associated Proteins
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Proteins/genetics/*metabolism
MH  - Receptor, trkB
MH  - Signal Transduction
PMC - PMC4035337
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/05/29 06:00
MHDA- 2015/08/14 06:00
PMCR- 2014/05/27
CRDT- 2014/05/29 06:00
PHST- 2013/10/21 00:00 [received]
PHST- 2014/05/06 00:00 [accepted]
PHST- 2014/05/29 06:00 [entrez]
PHST- 2014/05/29 06:00 [pubmed]
PHST- 2015/08/14 06:00 [medline]
PHST- 2014/05/27 00:00 [pmc-release]
AID - PONE-D-13-43024 [pii]
AID - 10.1371/journal.pone.0098687 [doi]
PST - epublish
SO  - PLoS One. 2014 May 27;9(5):e98687. doi: 10.1371/journal.pone.0098687. eCollection 
      2014.